Iron- and 2-oxoglutarate-dependent Dioxygenases: An emerging group of molecular targets for nickel toxicity and carcinogenicity

Haobin Chen, Max Costa

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Nickel compounds are important occupational and environmental pollutants. Chronic exposure to these pollutants has been connected with increased risks of respiratory cancers and cardiovascular diseases. However, it is still not clear what are the specific molecular targets for nickel toxicity and carcinogenicity. Here, we propose that the iron- and 2-oxoglutarate-dependent dioxygenase family enzymes are important intracellular targets that mediate the toxicity and carcinogenicity of nickel. In support of this hypothesis, our data show that three different classes of enzymes in this iron- and 2-oxoglutarate-dependent dioxygenase family, including HIF-prolyl hydroxylase PHD2, histone demethylase JHDM2A/JMJD1A, and DNA repair enzyme ABH3, are all highly sensitive to nickel inhibition. Inactivation of these enzymes accounts for a number of deleterious effects caused by nickel in cells, namely hypoxia-mimic stress and aberrant epigenetic changes. Future studies on nickel's effects on these iron- and 2-oxoglutarate-dependent dioxygenases would deepen our understanding on nickel toxicity and carcinogenicity.

Original languageEnglish
Pages (from-to)191-196
Number of pages6
JournalBioMetals
Volume22
Issue number1
DOIs
StatePublished - Feb 2009

Keywords

  • ABH3
  • Dioxygenase
  • Epigenetic
  • HIF
  • Histone methylation
  • Iron
  • JHDM2A/JMJD1A
  • Nickel

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